title: Imaging murine NALT following intranasal immunization with flagellin-modified circumsporozoite protein malaria vaccines.
abstract: Intranasal (IN) immunization with a Plasmodium circumsporozoite (CS) protein conjugated to flagellin, a Toll-like receptor 5 agonist, was found to elicit antibody-mediated protective immunity in our previous murine studies. To better understand IN-elicited immune responses, we examined the nasopharynx-associated lymphoid tissue (NALT) in immunized mice and the interaction of flagellin-modified CS with murine dendritic cells (DCs) in vitro. NALT of immunized mice contained a predominance of germinal center (GC) B cells and increased numbers of CD11c+ DCs localized beneath the epithelium and within the GC T-cell area. We detected microfold cells distributed throughout the NALT epithelial cell layer and DC dendrites extending into the nasal cavity, which could potentially function in luminal CS antigen uptake. Flagellin-modified CS taken up by DCs in vitro was initially localized within intracellular vesicles followed by a cytosolic distribution. Vaccine modifications to enhance delivery to the NALT and specifically target NALT antigen-presenting cell populations will advance development of an efficacious needle-free vaccine for the 40% of the world's population at risk of malaria.
authors.affiliation: 1] Division of Medical Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA [2] Present address: Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Nacer
authors.affiliation: 1] Division of Medical Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA [2] Present address: Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Carapau
authors.affiliation: Division of Medical Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: R
authors.initials: R
authors.lastname: Mitchell
authors.affiliation: Division of Medical Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Meltzer
authors.affiliation: 1] VaxInnate Corporation, Cranbury, New Jersey, USA [2] Present address: Vedantra Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
authors.forename: A
authors.initials: A
authors.lastname: Shaw
authors.affiliation: Division of Medical Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: U
authors.initials: U
authors.lastname: Frevert
authors.affiliation: Division of Medical Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Nardin
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005408:Flagellin / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D057054:Molecular Imaging; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D009305:Nasopharynx / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D005408:Flagellin